Pancreatic cancer (particularly, invasive pancreatic duct cancer) shows a mean survival time of approximately 6 months after diagnosis and is known to be intractable among malignant tumors. According to the vital statistics of population published by the Ministry of Health, Labour and Welfare of Japan, the annual number of deaths caused by pancreatic malignant tumors increases every year, and the number reached 26,791 according to the statistics of the year 2009. Furthermore, the proportion of deaths caused by pancreatic cancer occupied 9% of all cancer fatalities, and pancreatic cancer ranks the fifth after lung cancer, stomach cancer, colon cancer, and liver cancer.
According to the National Pancreatic Cancer Registration Investigation Report (year 1999), cases of resectable pancreatic cancer occupied 39% of all cases. Furthermore, the five-year survival rate is as low as 13%.
Regarding the reason why treatment of pancreatic cancer is difficult, one of the reasons may be that since there are only few subjective symptoms in the state of early stage, an early discovery is very difficult. In many cases, as cancer develops, symptoms such as abdominal pain, body weight reduction, and jaundice appear, and thereby cancer is discovered. Therefore, in a majority of cases, at the time of discovery by the manifestation of noticeable symptoms, the cancer is already in a state of advanced cancer without any surgical indications or limited to palliative operations.
Another reason why treatment is difficult may be that pancreatic cancer has characteristics of easily invading or metastasizing from the early stage. Another reason may be that since the pancreas is located at a retroperitoneal site and is positioned on the dorsal side of many intra-abdominal organs, during radiation therapy, it is difficult to irradiate only the diseased site of the pancreas with radiation. Therefore, radiation therapy has a high possibility of causing serious adverse side effects and may be excluded from applicable treatment options.
Currently, examples of the method for investigation or diagnosis of pancreatic cancer include examination methods such as biochemical examination of blood, abdominal ultrasonography, Endoscopic retrograde cholangiopancreatography (ERCP) examination, Computed Tomography (CT) combined with the use of a contrast agent, Magnetic resonance imaging (MRI), and a Positron Emission Tomography (PET) method (particularly, fluorodeoxy glucose (FDG)-PET method).
Meanwhile, in regard to the trend of utilizing peptides as biomaterials in the field of medicine, attention has been paid to cell membrane-permeable (cell-absorbable) peptides such as Tat, penetratin, and polyarginine.
However, since these peptides are generally and non-selectively absorbed without distinction between normal cells or normal tissues and tumor cells or tumor tissues, applying these peptides to therapeutic drug delivery system (DDS) tools for malignant tumors, where target-selective drug delivery is required, is not readily utilizable from the viewpoint of inducing serious adverse side effects. Particularly, cell membrane-permeable (cell-absorbable) peptides such as Tat, which are globally used in experimental systems, are known to have a property of accumulating in the liver (see, for example, Non-Patent Document 1).
In contrast, cyclic RGD is the only peptide that has been acknowledged as a medicine. Cyclic RGD is targeted at αvβ3 integrin, which has been reported to be expressed at a high level in the vascular endothelial cells that constitute new blood vessels or existing blood vessels (and some tumor cells) and has a point of action in vascular permeability enhancement. Therefore, cyclic RGD is applied as an imaging agent or a DDS preparation, not alone but in the form of simultaneous combined use with other drugs (see, for example, Patent Document 1).